Diabetes-impaired wound healing remains a major clinical complication. A major complication associated with diabetes is impaired wound healing or chronic ulcers. Many molecular and physiological factors contribute to the impairment in diabetic wound healing. For instance, lack of angiogenesis or irregular blood vessel network, excessive and prolonged inflammation, rampant oxidative stress, and senescence are commonly cited.[1-5; herein incorporated by reference in their entireties]. Therefore, therapies that can modulate these events are crucial in improving wound healing.
Sirtuin-1 (Sirt1), an NAD+-dependent lysine deacetylase, has been shown to regulate and restore angiogenic function and the secretion of proangiogenic factors in diabetic endothelial progenitor cell (EPC). [6, 7; herein incorporated by reference in their entireties] Seminal papers have demonstrated that Sirt1 is involved in the protection against excessive inflammation and oxidative stress by deacetylating NFκB and Forkhead box O transcription factors. [8, 9; herein incorporated by reference in their entireties] Furthermore, Sirt1 inhibits cellular senescence, promotes keratinocyte differentiation, and protects against UV-induced DNA damage.[10-13; herein incorporated by reference in their entireties] Several studies have demonstrated that Sirt1 is downregulated or dysfunctional in a diabetic milieu and that Sirt1 overexpression improves glucose intolerance and insulin sensitivity and protects against diabetes.[14-19; herein incorporated by reference in their entireties] However, the role of Sirt1 in diabetic foot ulcers or wound healing is not known.